LRX-1 is a poorly characterized cysteine-rich protein of unknown function in C. elegans. Despite its name suggesting "LRP cross-hybridizing", bioinformatic analysis reveals it is NOT a true LRP family member. The protein contains 30 cysteines (8.1% of sequence) in 17 potential cysteine-rich regions, but these do NOT form canonical LDL receptor Class A domains as incorrectly annotated. The protein lacks essential LRP features including Ξ²-propeller and EGF-like domains, and is much smaller (369 aa) than true LRP proteins (>4000 aa). Likely a secreted protein rather than membrane-bound, with C. elegans-specific cysteine-rich domains of unknown structure and function. High-throughput screens identified interactions with RSP-4, PFD-3, and PERM-4 (eggshell integrity protein), suggesting potential involvement in extracellular matrix organization, though biological significance remains unclear.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0012505 endomembrane system | IEA GO_REF:0000044 | REMOVE | Summary: ARBA-based prediction without experimental support Reason: Based on incorrect membrane protein prediction; bioinformatic analysis suggests secreted protein, not membrane-bound. Falcon deep research independently found no experimental evidence for any subcellular localization of lrx-1. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research-falcon.md direct primary experimental characterization of lrx-1/T04H1.6 (loss-of-function phenotypes, biochemical activity, or cellular localization) was not found |
| GO:0016020 membrane | IEA GO_REF:0000120 | REMOVE | Summary: ARBA-based prediction of membrane localization Reason: No strong transmembrane helix detected; weak hydrophobic regions incompatible with membrane insertion. Falcon deep research found no experimental localization data and states membrane/secreted assignment cannot be made beyond domain-based inference. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research-falcon.md Therefore, **primary function, substrate/ligand specificity, and site of action (tissue/subcellular)** cannot be stated beyond domain-based inference without overreach. file:worm/lrx-1/lrx-1-hypotheses/function-hypothesis-go-0016020/openscientist.md The GO:0016020 (membrane) annotation for *C. elegans* lrx-1 (UniProt Q22179) is **over-annotated** and should be removed. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000117 | REMOVE | Summary: ARBA-based prediction from incorrect LRP domain annotation Reason: Based on false LDL receptor domain predictions; no evidence for cargo receptor function. Falcon deep research explicitly states there is no evidence base to claim lrx-1 mediates endocytosis or binds lipoprotein ligands. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research-falcon.md Without direct lrx-1 experiments in the retrieved texts, it is not evidence-based to claim: - that lrx-1 binds cholesterol or specific lipoprotein ligands, - that it mediates endocytosis |
| GO:0003674 molecular_function | NAS | NEW | Summary: Added to align core_functions with existing annotations. The molecular function of LRX-1 is unknown; the previously proposed 'protein binding' (GO:0005515) term was uninformative and rested on a refuted LDL-A domain justification, so the root molecular_function term is used instead to reflect genuine uncertainty. Reason: Per curation guidelines, 'protein binding' (GO:0005515) is uninformative and should be avoided. Bioinformatic analysis shows LRX-1 has no canonical LDL-A domains, and Falcon deep research found no experimental evidence that lrx-1 binds any defined ligand or has any demonstrated molecular function. The high-throughput Y2H interactions are retained descriptively in the references but do not justify a specific MF annotation. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research-falcon.md Therefore, **primary function, substrate/ligand specificity, and site of action (tissue/subcellular)** cannot be stated beyond domain-based inference without overreach. file:worm/lrx-1/lrx-1-bioinformatics/RESULTS.md No canonical LDL-A domain patterns detected - Cysteine spacings are incompatible with LDL-A requirements |
| GO:0005576 extracellular region | IEA | NEW | Summary: Tentative extracellular/secreted localization inferred from sequence analysis (weak signal peptide, no transmembrane helix). Note that Falcon deep research found no experimental localization data, so this remains a prediction. Reason: Bioinformatic analysis predicts a secreted protein (weak N-terminal signal peptide, no transmembrane helix), favouring an extracellular localization over the removed membrane/endomembrane annotations. This is a sequence-based inference only; Falcon deep research explicitly states that the site of action cannot be established beyond domain-based inference, so the annotation is tentative. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research.md LRX-1 is a secreted, extracellular protein with a signal peptide directing it into the secretory pathway. It lacks transmembrane regions and is expected to reside in the extracellular matrix or periphery of cells file:worm/lrx-1/lrx-1-deep-research-falcon.md Therefore, **primary function, substrate/ligand specificity, and site of action (tissue/subcellular)** cannot be stated beyond domain-based inference without overreach. |
| GO:0009987 cellular process | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. |
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Download this section (compressed HTML)Q: How does LRX-1 regulate left-right asymmetry in C. elegans and what are its downstream targets?
Q: What determines the asymmetric expression pattern of LRX-1 and how is this established during development?
Q: How does LRX-1 interact with other transcription factors to control cell fate specification?
Q: What role does LRX-1 play in maintaining versus establishing asymmetric gene expression?
Experiment: Single-cell RNA sequencing of developing C. elegans embryos to map LRX-1 expression and target genes
Experiment: ChIP-seq analysis to identify direct LRX-1 binding sites across the genome
Experiment: Live imaging of LRX-1 expression during embryogenesis using fluorescent reporter constructs
Experiment: Functional analysis of LRX-1 binding site mutations to determine the cis-regulatory logic of asymmetric expression
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Download this section (compressed HTML)π View Pathway Visualization Interactive pathway diagram with detailed annotations